Halides, alkyl reaction with cyanohydrins

The anions of protected cyanohydrins are excellent nucleophiles in reaction with both primary and secondary alkyl halides. ... 

Reaction of (50) with alkyl halides gives exclusive a-alkylation. With aldehydes and ketones, a-addi-tion again takes place to give (52) via intramolecular silyl transfer with concomitant loss of lithium cyanide (c/. 25 Scheme 30). Treatment of (52) with p-Ts0H H20 gives the cyclopentenone annelation product. The allylic cyanohydrin anion (53) also gives a-adducts upon treatment with aldehydes and ketones at -78 °C, whereas reaction with electrophiles at 0 C affords -y-adducts (c/. 25). 

A number of methods for the generation of acyl anion equivalents from aldehydes have been developed. Related to the benzoin condensation, aldehyde cyanohydrins, protected as their ether derivatives, are readily transformed into anions by treatment with lithium diisopropylamide (LDA). Reaction with an alkyl halide gives the protected cyanohydrin of a ketone from which the ketone is liberated easily. Reaction with an aldehyde or ketone leads to the formation of an a-hydroxy ketone (1.109). ... 

This form of protection is advantageous for aldehydes, because the trimethylsilyl cyanohydrin ethers of aldehydes present a reactive hydrogen atom on the a carbon. This hydrogen can be replaced with lithium, after which the compound may be converted to a ketone by reaction with an alkyl halide, or it may be converted to an a-hydroxyketone by reaction with another aldehyde or ketone (Scheme 4.4) ... 

Most often, the application of cyanohydrin acetonide couplings to a natural product synthesis calls for coupling with a primary alkyl halide. This has proven successful in every instance. However, on occasion, alkylations of more hindered epoxides or hindered alkyl halides are desirable. These reactions are less dependable. 

Although nitriles lack an acyl group, they are considered acid derivatives because they hydrolyze to carboxylic acids. Nitriles are frequently made from carboxylic acids (with the same number of carbons) by conversion to primary amides followed by dehydration. They are also made from primary alkyl halides and tosylates (adding one carbon) by nucleophilic substitution with cyanide ion. Aryl cyanides can be made by the Sandmeyer reaction of an aryldiazonium salt with cuprous cyanide. a-Hydroxynitriles (cyanohydrins) are made by the reaction of ketones and aldehydes with HCN. 

Polymeric amines can be proton acceptors, acyl transfer agents, or ligands for metal ions. The 2- and 4-isomers of poly(vinylpyridine) (11) and (12) and the weakly basic ion exchange resins, p-dimethylaminomethylated PS (2) and poly(2-dimethylaminoethyl acrylate), are commercial. The ion exchange resins are catalysts for aldol condensations, Knoevenagel condensations, Perkin reactions, cyanohydrin formation and redistributions of chlorosilanes. " The poly(vinylpyridine)s have been used in stoichiometric amounts for preparation of esters from acid chlorides and alcohols, and for preparation of trimethylsilyl ethers and trimethylsilylamines from chlorotrimethylsilane and alcohols or amines. Polymer-suppored DBU (l,8-diazabicyclo[5.4.0]undec-7-ene) (52) in stoichiometric amounts promotes dehydrohalogenation of alkyl bromides and esterification of carboxylic acids with alkyl halides. The protonated tertiary amine resins are converted to free base form by treatment with aqueous sodium hydroxide. 

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